It is proposed to continue to study in depth the biochemical and morphologic basis for the development of liver cancer induced by ethionine, dimethylnitrosamine, acetylaminofluorene and some other hepatic carcinogens. Emphasis will be placed on DNA damage and repair as it relates to the effects of a single dose of carcinogen under conditions which do or do not lead to liver cancer and of repeated dietary intake of the carcinogen under conditions leading to cancer. Included in this will be the properties of DNA repair in hyperplastic nodules thought to be a precursor lesion for cancer. It is also planned to continue studies on the development of a differentiated liver cell system in vitro for use in chemical carcinogenesis in vitro.